tbuckley/cabot-search huggingface dataset:
Circulating tumor DNA in individuals with stomach adenocarcinoma (STAD) to detect MMR-related gene alterations.
Authors: Shi Zhang, Guoqiang Wang, Beiping Zhong, Name Fang, Aiwei Zhou, Minchao Liang, Yingqiang Li, Zhang Jing, Shaochen Cheng
Journal: Journal of Clinical Oncology (2023)

e16083 Background: Stomach adenocarcinoma (STAD) ranks as the second incidence rate in China. The MisMatch Repair (MMR), composed of MLH1, MSH2, MSH3, MSH6, and PMS2, is a critical mechanism for repairing DNA error. In case of microsatellite instability (MSI), the MMR system is capable of repairing the mismatches. MSI-high (MSI-H) is created as a result of deficient mismatch repair (dMMR). A numerous studies have established the clinical importance of both MSI and MMR for the diagnosis, prognosis, and treatment of STAD. Circulating tumor DNA (ctDNA) provides a non-invasive method for the diagnosis and prognosis of cancer. The examination of MMR-related gene mutations in STAD can serve as a means of evaluating the utility of ctDNA in detecting. Methods: MMR-related genes list was collected from relevant literature. The clinical and genetic mutation data of 441 STAD samples were obtained from cBioPortal. Kaplan-Meier survival analysis was used to evaluate the total survival rate (OS) of the published STAD data set. 680 STAD patients with TP53 mutation were screened and analyzed from the HapLab database. Results: An analysis of the TCGA data indicated that 356 patients had wild-type MMR genes and 85 had MMR mutations. MSH3 mutations accounted for 19.27% of the overall mutations and 42.35% of patients with MMR mutations, with a total of 36 patients. In terms of OS, patients with MMR gene mutations had a better prognosis compared to those with wild-type genes (log-rank test, p-value = 0.028). In the single-gene prognostic analysis, patients with MSH3 mutations had better prognosis (p-value 0.0004), while no statistical differences were found in other genes. In the monitoring of 680 HapLab STAD patients using ctDNA, 12.35% (84/680) had MMR mutations in their tumor tissue. After treatment, the proportion of TP53 mutations detected in patients was 11.91% (81/680), while the proportion of MMR mutations was 3.57% (3/84). Conclusions: The results of survival analysis showed a significant association between the mutation status of MMR and STAD. Monogenic MSH3 mutations was highly associated with the better survival, and circulating tumor DNA in blood highlight the importance of detecting MMR mutations in STAD patients. ctDNA provides a non-invasive method for the assessment of prognosis in STAD patients through the analysis of MMR gene mutations.
Health-related quality of life and economic burden in Chinese patients with cutaneous T-cell lymphoma.
Authors: Yang Wang, Jianfang Sun, Huiping Sun, Mingzhi Zhang, Zhiming Li, Haifeng Zhao, Linna Xie, Wenrong Huang, Xiaojing Yan, Xiwen Du, Xiaojiao Li, Hui Jin, Yuankai Shi
Journal: Journal of Clinical Oncology (2023)

e19533 Background: Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma. As described in European Organization for Research and Treatment of Cancer Consensus, the subtypes of mycosis fungoides (MF) and Sézary Syndrome (SS) comprised roughly 55% and 5% of CTCL, respectively. The clinical presentations of MF and SS include skin lesion, tumors, ulcerations, systemic involvements and even death. This study aimed to measure the overall HRQoL and economic burden of MF and SS patients in China. Methods: A cross-sectional survey was conducted from 21 July 2022 to 24 October 2022. Eligible adult participants with a pathologically confirmed diagnosis of either MF or SS were recruited from specialty or general hospitals across China. All participants were asked to complete a questionnaire that assessed HRQoL and annual economic burden. Validated instruments in Chinese, specifically the EuroQoL Group’s five-level QoL five-dimensional questionnaire (EQ-5D-5L), Functional Assessment of Cancer Therapy-General (FACT-G), and Skindex-29, were used to assess general, cancer and skin-related HRQoL. All HRQoL outcomes were calculated using the scoring system provided by the institutions, and EQ-5D utility scores were mapped using the China time trade-off value sets. As for economic burden, it was investigated from the societal perspective, as the direct medical costs, direct non-medical costs, and productivity loss were all calculated. Results: A total of 61 patients were recruited and completed the survey. Patients resided in 38 cities of 21 provinces across China. 56 patients (92%) were diagnosed with MF and 5 (8%) with SS. 56% were male, with a mean age of 39 years. Half of the patients had early-stage disease (defined as less than stage IIB, patch or plaque), with the remainder having late-stage disease. Among the recruited patients, 43 (70%) received skin-directed therapy, and 55 (90%) received systemic therapy. As for HRQoL measures, EQ-5D utility score was 0.79 (±0.18), FACT-G score was 61.3 (±12.4), and the Skindex-29 score was 43.4 (±24.2). Comparison between patients with early-stage disease and late-stage is presented in the table. As for economic burden, the annual per capita cost for MF and SS patients was CNY 86,729 (USD 12,428), which greatly exceeded the annual disposable income in 2022 (CNY 36,883, equals USD 5,440). Conclusions: This was the first study investigating economic burden and HRQoL using patient-reported outcomes conducted in mainland China. The findings suggested that MF and SS has significantly compromised patients’ HRQoL and posed substantial economic burden. [Table: see text]
Real-world response rates and clinical outcomes of patients treated with first-line (1L) platinum-based chemotherapy (PBC) in advanced urothelial cancer (aUC).
Authors: Helen H Moon, Jeanny B. Aragon-Ching, Allison Thompson, Anup Abraham, Anna Vlahiotis, Chiemeka Ike, Darrin Benjumea, Anran Shao, Haiyan Sun, Mairead Kearney, Norbek Gharibian, Sarah Hanson, Benjamin Li, Melissa Kirker, Petros Grivas
Journal: Journal of Clinical Oncology (2023)

4567 Background: Standard of care has been established as 1L PBC followed by avelumab 1L maintenance (1LM) in eligible pts based on the JAVELIN Bladder 100 trial (NCT02603432) which showed that avelumab 1LM significantly prolonged overall and progression-free survival (OS, PFS) in pts with aUC with no disease progression after 1L PBC. Contemporary and robust real-world (rw) data are limited in pts treated with 1L PBC; however, because response status to PBC determines avelumab 1LM eligibility, it is critical to understand rwR rates. This study aimed to assess current rwR rates and rw outcomes in pts treated with 1L PBC. It also sought to understand avelumab 1LM eligibility and its early utilization since FDA approval on June 30, 2020. Methods: A non-interventional, retrospective cohort study of pts with aUC in the US was conducted using data from Flatiron Health’s electronic health record database. Pts were included if they were diagnosed with aUC between Jan 1, 2017, and Sep 30, 2021, received 1L PBC, did not have a progression event and had an observed rwR (complete response [rwCR]/partial response [rwPR]) or stable disease (rwSD) during 1L. Pt characteristics and rw outcomes were described based on response type (rwCR/PR, rwSD); rwPFS and rwOS were measured from time of 1L PBC initiation using the Kaplan-Meier method. Results: 1,245 pts with aUC received 1L PBC and had rwR data available during study period. Of these, 80% (n=998) may have been eligible to receive avelumab 1LM (rwCR/PR: 60%, rwSD: 20%). Key characteristics and outcomes by rwR are summarized. During the study period that occurred after FDA approval of avelumab 1LM, 435 pts discontinued 1L PBC, 78% (n=339) of these pts had observed rwCR/PR/SD during 1L PBC, and 29% (n=97) of maintenance eligible pts received avelumab 1LM. Follow-up time for avelumab 1LM treated pts was short (median 7.5 months from initiation of 1LM) and outcomes were immature at the end of the study period. Conclusions: In this rw study, a large proportion of pts with aUC treated with 1L PBC had rwR or rwSD (≈80%) and may have been eligible for avelumab 1LM, which is the standard of care supported by international guidelines. RwR rate appears slightly higher compared to historic data, and may reflect better general patient care, as shown in recent large phase 3 trials (NCT02853305, NCT02516241, NCT02807636). Early uptake of avelumab 1LM was observed, and future studies with longer follow-up may demonstrate increased utilization and allow assessment of potential impact on outcomes. [Table: see text]
Validation of the PDACai signature in predicting relative benefit from frontline FOLFIRINOX (FFX) and gemcitabine/nab-paclitaxel (GA) for patients (pts) with metastatic pancreatic cancer (mPDAC).
Authors: Michael J. Pishvaian, Edik Matthew Blais, Dzung Thach, Jonathan Robert Brody, Lynn McCormick Matrisian, David Charles Halverson, Patricia DeArbeloa, Flavio G Rocha, Andrew Eugene Hendifar, Emanuel Petricoin
Journal: Journal of Clinical Oncology (2023)

4149 Background: Nearly 50% of pts with mPDAC never receive a 2nd line of therapy for metastatic disease following frontline FFX or GA. Genomic alterations in the DDR pathway (e.g. BRCA1/2) are associated with increased progression-free survival (PFS) on platinum-containing regimens (e.g. FFX), but other biomarker-treatment associations that predict benefit from GA and/or FFX in mPDAC remain unexplored. In this retrospective real-world evidence (RWE) study, we use a data-driven machine learning approach to gain new insights from the mutational landscape in mPDAC and validate the PDACai signature in predicting personalized benefit from both FFX and GA. Methods: We analyzed real-world outcomes from 711 pts with mPDAC who underwent genomic profiling via the Know Your Tumor program or were referred to Perthera by treating oncologists. Chart-abstracted PFS data on either 1st line FFX or GA were split (60:40) into independent training and validation cohorts for each regimen. All models integrate a shared set of clinical (age &lt; 63, sex) and lab-agnostic molecular features derived from clinical NGS testing reports (DDR pathway alterations, specific KRAS variants, frequently mutated genes). Relative benefit scores predicted by FFX or GA models were evenly binned into three PDACai signature categories representing lower, middle, and upper tertiles for each independent cohort. Statistical differences in median PFS were evaluated using ordinal Cox regression. Results: Median PFS followed predicted trends as generated by PDACai for each therapy in training and validation cohorts. The predictive utility of PDACai was confirmed in the independent validation cohorts when comparing PFS on FFX (p = 0.03744; HR = 0.75 [95% CI: 0.58-0.98]) and GA (p = 0.00006861; HR = 0.65 [95% CI: 0.53-0.8]) across tertiles. Conclusions: Response to chemotherapy is heterogeneous and difficult to predict in pts with mPDAC. Using RWE, the PDACai signature successfully predicted relative differences in PFS on both FFX and GA in mPDAC. With prospective validation, personalized insights generated by PDACai from pts with similar biomarker profiles could be used to tailor treatment sequencing in pts with NGS testing results, particularly those without actionable genomic findings. [Table: see text]
Chemoradiotherapy with concurrent durvalumab for the palliative treatment of oligometastatic esophageal and gastroesophageal carcinoma with dysphagia: A single arm phase 2 clinical trial, PALEO.
Authors: Fiona Day, Swetha Sridharan, Michael Michael, Louise Christophersen, Melissa M. Moore, Melissa A. Eastgate, Stephen Thompson, ANGELA MWEEMPWA, Christopher Oldmeadow, Allison Fraser, Jarad Martin
Journal: Journal of Clinical Oncology (2023)

TPS4172 Background: Many patients diagnosed with esophageal cancer have dysphagia from their primary tumor and de novo metastatic disease. While multiple therapies are available, there is no accepted standard or sequence of therapies to both relieve dysphagia and control distant disease. Our preceding Phase I clinical trial showed that a 2 week hypofractionated chemoradiotherapy (CRT) protocol (30Gy/10# with concurrent weekly carboplatin and paclitaxel) is well tolerated and provides rapid dysphagia relief. Immune checkpoint inhibition has activity in esophageal and gastroesophageal (GEJ) cancer and concurrent radiotherapy may improve T cell priming through tumor antigen release. In PALEO, patients begin durvalumab concurrent with primary tumor CRT, and receive stereotactic body radiotherapy (SBRT) (24Gy/3#) to a single metastasis to maximize the breadth of tumor antigen exposure. Tissue and blood-based studies are planned to identify biomarkers for response, including immunosequencing to test for post-radiotherapy expansion in T cell receptor diversity. Methods: Eligible patients have biopsy-proven esophageal or GEJ cancer, either squamous cell or adenocarcinoma histology, with oligometastatic (1-5 metastases on FDG-PET scan outside the primary tumor radiotherapy field) or locoregionally advanced disease unsuitable for surgery, dysphagia (Mellow score &gt;0), and ECOG PS 0-2. Key exclusion criteria are prior treatment, tumor HER2 positivity, prior thoracic radiotherapy, tracheo-esophageal fistula, esophageal stent in situ and contraindications to immunotherapy. Patients begin durvalumab 1500mg q4w with CRT to the primary tumour (30Gy/10# with weekly carboplatin AUC2 and paclitaxel 50mg/m2), and continuing to disease progression, unacceptable toxicity or 2 years. SBRT to one metastasis (24Gy/3#) is delivered in week 7. Trial primary endpoint is progression free survival rate at 6 months (PFS6) with the aim to rule out a PFS6 rate of 50% in favor of 67.5%, with 80% power and a one-sided 0.05 significance level. Secondary endpoints include dysphagia relief, nutritional status change (patient weight, removal of enteral feeding tubes, PG-SGA score), quality of life, response rate, toxicity, overall survival and exploratory translational endpoints. PALEO is sponsored by the Australasian Gastro-Intestinal Trials Group (AGITG) for conduct at 8 sites in Australia and New Zealand. 6 of planned 54 patients have been enrolled. ACTRN12619001371189. Clinical trial information: Clinical trial information: ACTRN12619001371189 .
Enhancement in line of therapy (LoT) derivation from real-world data (RWD) from electronic health records (EHR) via integration of medical claims data.
Authors: Smita Agrawal, Avinash P B, Rohini George, Neeraj Singh, Megha Soni, Sangavai Chakkrapani, Vandana Priya, Vivek Prabhakar Vaidya
Journal: Journal of Clinical Oncology (2023)

6514 Background: Clinical RWD derived from EHRs is becoming increasingly important for clinical research, trial design, regulatory decisions etc. These applications require identification of lines of therapy (LoT) which are typically not captured in EHR and must be abstracted from other clinical and medication data. EHR data has significant missingness which can be complemented with other data sources such as medical claims data. In this study, we demonstrate how our proprietary line of therapy algorithms for solid cancers show significant improvements when built using integrated EHR and claims data when compared to EHR data alone. Methods: For this analysis, ConcertAI’s RWD360 dataset integrated with a large administrative open-claims dataset (&gt;90% overlap) for 14 solid cancer indications (Breast, Bladder, Lung, Prostate, Pancreas, Melanoma, Liver, Head &amp; Neck, Renal, Colorectal, Melanoma, Ovarian, Thyroid, Endometrial) was used. The date of advanced/metastatic diagnosis used as the index date for LoTs was derived from the EHR data and medications from both EHR and claims data were used. We ran our LoT algorithms on EHR data with and without claims data and evaluated the impact of integrating claims data on the quantity and quality of LoT output. Results: The inclusion of medication data from claims significantly increased (7-22%) the number of patients for which LoTs could be extracted from the EHR data. Furthermore, we observed increases in number of lines per patient, length of lines and medications per line across cohorts. The distance between index date and 1st line start date was shortened in a subset (2-12%) of patients as a result. In a small fraction of cases, we even observed removal of false lines as some of the lines moved to adjuvant/neoadjuvant setting by filling in missing medication from claims. Overall, 7-39% patients in the LoT cohorts were impacted by addition of claims. Results for a few cancer types are presented in Table 1. We also compared the top LoTs derived from the integrated dataset against the standard of care for that cancer and observed very good concordance. Conclusions: Deriving LoTs by integrating data from multiple data sources such as EHR and claims can significantly improve its accuracy. [Table: see text]
Randomized placebo-controlled trial of intravenous vitamin C plus docetaxel in metastatic prostate cancer.
Authors: Channing Judith Paller, Marianna Zahurak, Elisabeth I. Heath, William Kevin Kelly, Christopher J. Hoimes, Jason David Taksey, Catherine Handy Marshall, Mark Christopher Markowski, Pedro C. Barata, Michelle A. Rudek, Julie Nauroth, Lin Wang, Jennifer N. Durham, Mario A. Eisenberger, Michael Anthony Carducci, Samuel R. Denmeade, Mark Levine
Journal: Journal of Clinical Oncology (2023)

e17050 Background: Some phase I/II trials showed that combining high dose IV vitamin C with chemotherapies decreased toxicities and improved QoL in advanced cancers, while others failed to show benefits. While grade ¾ AEs are not typically a co-primary endpoint, they are a measure of cumulative toxicity. We investigated whether high-dose IV vitamin C could improve prostate-specific antigen (PSA) response rate and mitigate docetaxel toxicities in patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving docetaxel. Methods: Patients were randomized (2:1) to receive docetaxel (75mg/m2 IV every 3 weeks) plus IV vitamin C (1g/kg) or placebo twice a week. The primary endpoints were PSA50 response by24 weeks and adverse events (AEs) of fatigue, nausea, bone pain, and anorexia. Secondary endpoints included overall survival (OS) and QoL measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Results: 50 patients were randomized, 47 received therapy (treatment N = 32, control N = 15), 3 untreated (withdrawal, elevated creatine, low hemoglobin). The median age was 74 years (range 45-85) and ECOG 1. The median PSA was 108.3 ng/mL (range: 0.3, 2102.3). The median number of chemotherapy cycles was 6 (IQR 3-8). The study was suspended after the pre-specified interim analysis for primary endpoints showed futility. The PSA50 response was 41% for treatment and 33% for control (P = 0.44). Grade 1-2 and grade 3-4 prespecified AEs occurred in 69% and 6% of treatment group patients versus 60% and 0% of control group patients (one-sided Cochran Armitage test, P =0.90). Diarrhea (72% vs 19%) and anemia (47% vs 25%) and neutropenia (22% vs 19%) are more frequent in the Vit C group. Compared with the control group, treatment group patients showed a trend towards shorter median OS. FACT-P was not significantly different at any timepoints. Conclusions: Initial concurrent high-dose IV vitamin C with docetaxel did not improve PSA response, toxicity, or clinical outcomes. MCRPC patients receiving docetaxel should be advised against seeking concurrent high-dose IV vitamin C. Clinical trial information: NCT02516670 .
Association of the Duffy-null allele and endometrial cancer characteristics: An effort to explore racial disparity in Black women with endometrial cancer.
Authors: Emily M. Webster, Rachel Martini, Amita Kulkarni, Priyanka Narayan, Max Chao, Evelyn Cantillo, Melissa Kristen Frey, Kevin Holcomb, Olivier Elemento, Melissa Davis, Eloise Chapman-Davis
Journal: Journal of Clinical Oncology (2023)

5603 Background: Efforts are needed to identify factors that account for the disparately high mortality in Black women with endometrial cancer. The Duffy antigen receptor for chemokines (DARC) is expressed on erythrocytes and endothelial cells and modulates levels of inflammatory chemokines in circulation and in tissues. The African ancestry-specific Duffy-null allele, in which erythrocyte expression and function of DARC is lost, is associated with worse breast cancer phenotypes and survival. Here, we characterize Duffy-null status and associated prognostic and clinical outcomes in patients with endometrial cancer. Methods: Patients with endometrial cancer were prospectively consented, and germline DNA was extracted from saliva or blood samples. Duffy-null genotype was determined using an allelic discrimination assay. Associations between Duffy-null genotype status and clinicopathologic characteristics were performed using Fisher’s Exact analysis. Results: 33 patients were enrolled (Table); 17 (51.5%) were Duffy-null, 5 (15.2%) were Duffy-null allele carriers, and 11 (33.3%) were non-carriers. Compared with non-carriers, Duffy-null patients were more likely to be Black (100% v 9.1%, p&lt;0.0001) and have non-endometrioid histology (64.7% v 10%, p=0.0173). There was a trend towards higher rates of grade 3 histology (70.6% v 36.6%), intact tumor mismatch repair (MMR) (86.7% v 54.6%), estrogen receptor (ER) negative tumor status (25% v 10%), advanced stage (37.5% v 18.2%), and positive lymph nodes (25% v 0%) (Table). Over a minimum of 12 months of follow up, only Duffy-null individuals died from disease (4 v 0, p=0.0006). Conclusions: Duffy-null status was associated Black race, aggressive histologic subtypes, intact MMR mechanisms, and worse survival. Further investigation is needed to explore the underlying mechanism of the Duffy-null phenotype on endometrial cancer outcomes to better elucidate risk factors and underlying causes that may contribute to endometrial cancer disparities.[Table: see text]